Sabourin, Prepr. Div. Pet. Chem., Am. Chem. Soc., vol. 24, pp. 233-239 discloses the preparation of 2-methyl-4-(3-aminophenyl)-3-butyn-2-ol (an aminophenylacetylene) and 3-aminophenylacetylene in two and three steps, respectively, from 3-bromonitrobenzene and 2-methyl-3-butyn-2-ol. In the first step, 3-bromonitrobenzene and 2-methyl-3-butyn-2-ol were reacted in the presence of a catalyst system of bis(triphenylphosphine)palladium dichloride, additional triphenylphosphine, and cuprous iodide in triethylamine solvent at the reflux temperature to obtain 2-methyl-4-(3-nitrophenyl)-3-butyn-2-ol. In the second step, this nitrophenylacetylene was hydrogenated in isopropanol in the presence of a Ru/Al.sub.2 0.sub.3 catalyst to obtain 2-methyl-4-(3-aminophenyl)-3-butyn-2-ol. This reference states that is essential to stop the hydrogenation reaction at the stoichiometric point because reduction of the triple bond ensues. In the third step, this aminophenylacetylene was heated in toluene in the presence of sodium hydroxide pellets, with removal of the acetone co-product by distillation, to obtain 3-aminophenylacetylene.
This reference also discloses an attempt to similarly react 3-bromoaniline, instead of 3-bromonitrobenzene, with 2-methyl-3-butyn-2-ol to obtain 2-methyl-4-(3-aminophenyl)-3-butyn-2-ol directly, and reports that 3-bromo-aniline failed to react at any appreciable rate at temperatures up to ca. 100.degree. C.
U.S. Pat. Nos. 4,128,588 and 4,204,078 (each also from the same Sabourin as inventor, with Selwitz) also discloses this preparation of 2-methyl-4-(3-nitrophenyl)-3-butyn-2-ol from 3-bromonitrobenzene and 2-methyl-3-butyn-2-ol. U.S. Pat. No. 4,139,561 and J. Org. Chem., vol. 44 (1979), pp. 1223-1236 (both Onopchenko as well as the same Sabourin and Selwitz) also discloses the preparation of 2-methyl-4-(3-aminophenyl)-3-butyn-2-ol from 2-methyl-4-(3-nitrophenyl)-3-butyn-2-ol by hydrogenation with a ruthenium catalyst, and its subsequent conversion to 3-aminophenylacetylene. Both the patent and journal disclosures highlight the difficult challenge of selectively hydrogenating the nitro group in the presence of the acetylene group. Subsequent U.S. Pat. Nos. 4,215,226; 4,216,341; 4,219,679 and a publication J. Org. Chem., vol. 44 (1979), pp. 3671-3674 from Onopchenko, Sabourin, and Selwitz disclose hydrogenations of 2-methyl-4-(3-nitrophenyl)-3-butyn-2-ol to 2-methyl-4-(3-aminophenyl)-3-butyn-2-ol using other hydrogenation catalysts.
Synlett, 1995, pp. 1115-1116 discloses this preparation of 2-methyl-4-(4-nitrophenyl)-3-butyn-2-ol from 4-bromonitrobenzene and 2-methyl-3-butyn-2-ol in high yield using a catalyst system comprising palladium on carbon, triphenylphosphine, and cuprous iodide in the presence of 2.5 equivalents of potassium carbonate in 1:1 1,2-dimethoxyethane:water at 80.degree. C. This reference also discloses the preparation of 2-methyl-4-(3-aminophenyl)-3-butyn-2-ol in 78% isolated yield from 3-iodoaniline (in place of 4-bromonitro-benzene) using the same system and the same conditions. The reference does not disclose any attempt to similarly react 3-bromoaniline.